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Stoichiometry for α-bungarotoxin block of α7 acetylcholine receptors

Author

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  • Corrie J. B. daCosta

    (Mayo Clinic College of Medicine
    Present address: Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie-Curie, Ottawa, Ontario, Canada K1N 6N5.)

  • Chris R. Free

    (Mayo Clinic College of Medicine)

  • Steven M. Sine

    (Mayo Clinic College of Medicine
    Mayo Clinic College of Medicine)

Abstract

α-Bungarotoxin (α-Btx) binds to the five agonist binding sites on the homopentameric α7-acetylcholine receptor, yet the number of bound α-Btx molecules required to prevent agonist-induced channel opening remains unknown. To determine the stoichiometry for α-Btx blockade, we generate receptors comprised of wild-type and α-Btx-resistant subunits, tag one of the subunit types with conductance mutations to report subunit stoichiometry, and following incubation with α-Btx, monitor opening of individual receptor channels with defined subunit stoichiometry. We find that a single α-Btx-sensitive subunit confers nearly maximal suppression of channel opening, despite four binding sites remaining unoccupied by α-Btx and accessible to the agonist. Given structural evidence that α-Btx locks the agonist binding site in an inactive conformation, we conclude that the dominant mechanism of antagonism is non-competitive, originating from conformational arrest of the binding sites, and that the five α7 subunits are interdependent and maintain conformational symmetry in the open channel state.

Suggested Citation

  • Corrie J. B. daCosta & Chris R. Free & Steven M. Sine, 2015. "Stoichiometry for α-bungarotoxin block of α7 acetylcholine receptors," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9057
    DOI: 10.1038/ncomms9057
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    Cited by:

    1. Christian J. G. Tessier & Johnathon R. Emlaw & Raymond M. Sturgeon & Corrie J. B. daCosta, 2023. "Derepression may masquerade as activation in ligand-gated ion channels," Nature Communications, Nature, vol. 14(1), pages 1-8, December.

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